In the U.S., prostate cancer has the highest prevalence among cancers in males. In Japan too, the prevalence of the prostate cancer is consistently increasing due to the change of lifestyle such as westernization of dietary life (Non-patent Literature 1). Since no specific symptoms are manifested in the early stage of prostate cancer, and since prostate cancer is often complicated with benign prostatic hyperplasia, the symptoms similar to those of benign prostatic hyperplasia, and dysuria, nocturia, urinary urgency and the like are found in some cases. Therefore, recently, even though no symptom is observed, most of prostate cancer is detected by measurement of PSA prostate-specific antigen in the blood in medical examination or health screening. Prostate cancer is characterized by high frequency of metastasis, and in some cases, advanced cancer is found because of low back pain due to bone metastasis (Non-patent Literature 2).
As the factor deciding the prognosis of prostate cancer, stage (in the following) thereof before surgery is important.
Stage A: cases where prostate cancer was accidentally found in surgery of benign prostatic hyperplasia or bladder cancer
Stage B: cases where the cancer is confined in the prostate
Stage C: cases where the cancer is not metastasized to other organs (such as bone, lymph node, lung and liver), but the cancer is exposed to the outside of the coating membrane (the membrane coating the periphery of prostate)
Stage D: cases where the cancer is metastasized to other organs such as bone and lymph node
For the cases of Stage A to Stage C, basically, total extirpation of prostate is carried out. However, in a considerable number of cases, recurrence of the cancer within several years after the surgery is observed. Especially, refractoriness to hormone therapy and metastasis are important factors which aggravate the survival prognosis, so that to estimate these factors at an early stage has a great clinical significance in the selection of therapy or treatment of the patient. However, up to now, no molecular marker is known which enables to estimate the prognosis of prostate cancer, especially the metastasis thereof, at an early stage.
On the other hand, it is known that blockade of NF-κB (nuclear factor, NF)-κB) activity, which is one of the transcription factors, inhibits angiogenesis, infiltration and metastasis in human prostate cancer (Non-patent Literature 3). More particularly, Non-patent Literature 3 discloses that when a mutated IκBα gene having an activity to inhibit NF-κB activity was introduced into metastatic human prostate cancer cells PC-3M and the cells were transplanted to nude mice, angiogenesis, infiltration and metastasis were inhibited in the group wherein NF-κB activity was reduced by the introduction of the mutated IκBα gene when compared with the group wherein the human prostate cancer cells PC-3M into which the mutated IκBα gene was not introduced were transplanted. Non-patent Literature 4 discloses that in prostate cancer cells, expression of NF-κB significantly occurs in the nuclei. Non-patent Literature 5 discloses that by the action of Pin1 which is a type of peptidyl-prolyl isomerase that specifically acts on the sequence of phosphorylated threonine or serine and subsequent proline, which sequence exists in a protein, on p65/RelA which is a subunit of NF-κB and in which the 254th amino acid threonine is phosphorylated, the binding of NF-κB-p65/RelA to IκBα that is an inhibition factor of NF-κB is inhibited, so that nuclear accumulation and stability of NF-κB-p65/RelA are increased and, in turn, the NF-κB activity is increased.    Non-patent Literature 1: Wakai K. Descriptive epidemiology of prostate cancer in Japan and Western countries Nippon Rinsho. 2005 February; 63(2):207-12.    Non-patent Literature 2: Loberg R D, Gayed B A, Olson K B, Pienta K J. A paradigm for the treatment of prostate cancer bone metastases based on an understanding of tumor cell-microenvironment interactions. J Cell Biochem. 2005 Oct. 15; 96(3):439-46.    Non-patent Literature 3: Huang S, Pettaway C A, Uehara H, Bucana C D, Fidler I J. Blockade of NF-kappaB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion, and metastasis. Oncogene. 2001 Jul. 12; 20(31):4188-97.    Non-patent Literature 4: Lessard L, Begin L R, Gleave M E, Mes-Masson A M, Saad F. Nuclear localisation of nuclear factor-kappaB transcription factors in prostate cancer: an immunohistochemical study. Br J Cancer. 2005 Oct. 31; 93(9):1019-23.    Non-patent Literature 5: Ryo A, Suizu F, Yoshida Y, Perrem K, Liou Y C, Wulf G, Rottapel R, Yamaoka S, Lu K P. Regulation of NF-kappaB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA. Mol Cell. 2003 December; 12(6):1413-26.